The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation.

BACKGROUND: Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin's effects on cognitive function have not been widely or systematically studied. AIM: The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. Primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel, and emotional processing scales. Safety was assessed via endpoints which included cognitive function, assessed by CANTAB global composite score, and treatment-emergent adverse event (TEAE) monitoring. METHODS: In this phase 1, randomised, double-blind, placebo-controlled study, healthy participants (n = 89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support - each participant having an assigned, dedicated therapist available throughout the session. RESULTS: In total, 511 TEAEs were reported, with a median duration of 1.0 day; 67% of all TEAEs started and resolved on the day of administration. There were no serious TEAEs, and none led to study withdrawal. There were no clinically relevant between-group differences in CANTAB global composite score, CANTAB cognitive domain scores, or emotional processing scale scores. CONCLUSIONS: These results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing. CLINICAL TRIAL REGISTRATION: EudraCT (https://www.clinicaltrialsregister.eu/) number: 2018-000978-30.

The Psychological Pathway to Suicide Attempts: A Strategy of Control Without Awareness.

OBJECTIVES: This paper aims to identify potential areas for refinement in existing theoretical models of suicide, and introduce a new integrative theoretical framework for understanding suicide, that could inform such refinements. METHODS: Literature on existing theoretical models of suicide and how they contribute to understanding psychological processes involved in suicide was evaluated in a narrative review. This involved identifying psychological processes associated with suicide. Current understanding of these processes is discussed, and suggestions for integration of the existing literature are offered. RESULTS: Existing approaches to understanding suicide have advanced the current knowledge of suicide in various ways. They have guided valuable research in the following areas: motivations for suicide and the psychological distress which influences suicide attempts; ambivalence about suicide; suicidal individuals' focus of attention; and ways in which individuals who contemplate suicide differ from individuals who attempt suicide. We outline a new theoretical framework as a means to integrating all of these concepts into the three principles of control, conflict, and awareness. Within this framework, suicide is regarded as occurring due to a long standing conflict between an individual's personal goals, culminating in an episode of acute loss of control. The new framework posits that the individual then strives to regain control through the means of suicide because of a narrowed awareness of consequences of their actions on other valued goals. This psychological mechanism of limited awareness is posited to be the common pathway by which individuals make a suicide attempt, regardless of which risk factors are present. CONCLUSION: This article introduces a theoretical framework that generates several hypotheses for future research, and focuses on psychological processes occurring during immediate crisis. One of the key hypotheses resulting from our predictions on how individuals progress from contemplating to attempting suicide will be tested in an ongoing program of research: Individuals who attempt suicide have a significantly reduced awareness of consequences of suicide, which would negatively impact on their important life goals, values, principles, or ideals, compared to individuals who contemplate suicide. Therapy guided by the new framework may be more flexible, immediate, and client-focused than other therapies for suicidal individuals.

Development and Evaluation of a Therapist Training Program for Psilocybin Therapy for Treatment-Resistant Depression in Clinical Research.

Introduction: Psychological support throughout psilocybin therapy is mandated by regulators as an essential part of ensuring participants' physical and psychological safety. There is an increased need for specially trained therapists who can provide high-quality care to participants in clinical studies. This paper describes the development and practical implementation of a therapist training program of psychological support within a current phase IIb international, multicenter, randomized controlled study of psilocybin therapy for people experiencing treatment-resistant depression. Description of Training Program: This new and manualized approach, based on current evidence-based psychotherapeutic approaches, was developed in partnership with different mental health researchers, practitioners, and experts; and has been approved by the FDA. Training consists of four components: an online learning platform; in-person training; applied clinical training; and ongoing individual mentoring and participation in webinars.This paper provides a brief overview of the method of support, the rationale and methodology of the training program, and describes each stage of training. The design and implementation of fidelity procedures are also outlined. Lessons Learned: As part of the phase IIb study of psilocybin therapy for treatment-resistant depression, 65 health care professionals have been fully trained as therapists and assisting therapists, across the US, Canada and Europe. Therapists provided informal feedback on the training program. Feedback indicates that the didactic and experiential interactive learning, delivered through a combination of online and in-person teaching, helped therapists build conceptual understanding and skill development in the therapeutic approach. Clinical training and engagement in participant care, under the guidance of experienced therapists, were considered the most beneficial and challenging aspects of the training. Conclusions: Clinical training for therapists is essential for ensuring consistently high-quality psilocybin therapy. Development of a rigorous, effective and scalable training methodology has been possible through a process of early, active and ongoing collaborations between mental health experts. To maximize impact and meet phase III and post-approval need, enhanced online learning and establishing pathways for clinical training are identified as critical points for quality assurance. This will require close public, academic and industry collaboration.

How did mental health become so biomedical? The progressive erosion of social determinants in historical psychiatric admission registers.

This paper explores the historical developments of admission registers of psychiatric asylums and hospitals in England and Wales between 1845 and 1950, with illustrative examples (principally from the archives of the Rainhill Asylum, UK). Standardized admission registers have been mandatory elements of the mental health legislative framework since 1845, and procedural changes illustrate the development from what, today, we would characterize as a predominantly psychosocial understanding of mental health problems towards primarily biomedical explanations. Over time, emphasis shifts from the social determinants of admission to an asylum to the diagnosis of an illness requiring treatment in hospital. We discuss the implications of this progressive historical diminution of the social determinants of mental health for current debates in mental health care.

Method of levels therapy for first-episode psychosis: The feasibility randomized controlled Next Level trial.

OBJECTIVE: We aimed to determine the feasibility and acceptability of Method of Levels (MOL) for people experiencing first-episode psychosis (FEP) to inform decision making about the therapy's suitability for further testing in a larger clinical trial. METHOD: A parallel group randomized controlled trial design was used. Participants (N = 36) were allocated to receive either treatment as usual (TAU) or TAU plus MOL. Recruitment and retention in the trial and the acceptability of the MOL intervention were the primary outcomes. RESULTS: The recruitment target was met within the planned time frame. Retention in the trial at final follow-up was 97%, substantially higher than the 80% threshold prespecified as a successful feasibility outcome. Participant feedback provided initial evidence of the acceptability of the study design and intervention for this population. CONCLUSION: Results support progressing to a larger trial of MOL for FEP. Recommendations for the design of future trials are provided.

Method of levels therapy for first-episode psychosis: rationale, design and baseline data for the feasibility randomised controlled Next Level study.

BACKGROUND: Method of levels (MOL) is an innovative transdiagnostic cognitive therapy with potential advantages over existing psychological treatments for psychosis. AIMS: The Next Level study is a feasibility randomised controlled trial (RCT) of MOL for people experiencing first-episode psychosis. It aims to determine the suitability of MOL for further testing in a definitive trial (trial registration ISRCTN13359355). METHOD: The study uses a parallel group non-masked feasibilityRCT design with two conditions: (a) treatment as usual (TAU) and (b) TAU plus MOL. Participants (n = 36) were recruited from early intervention in psychosis services. Outcome measures are completed at baseline, 10 and 14 months. The primary outcomes are recruitment and retention. RESULTS: Participants' demographic and clinical characteristics are presented along with baseline data. CONCLUSIONS: Next Level has recruited to target, providing evidence that it is feasible to recruit to a RCT of MOL for first-episode psychosis. DECLARATION OF INTEREST: None.

What is distressing about auditory verbal hallucinations? The contribution of goal interference and goal facilitation.

OBJECTIVES: Distressing and pleasant/positive voices (auditory verbal hallucinations) are common in both clinical and non-clinical voice-hearers. Identifying factors that contribute to emotional reactions to voices is essential for developing effective psychological interventions. Several theories propose that facilitation and interference with personal goals are important predictors of distress and well-being. This study examined whether voice-related distress is related to the degree to which voices interfere with personal goals, and whether pleasantness of voices is influenced by the extent to which they facilitate goals. DESIGN: Cross-sectional with clinical and non-clinical voice-hearers. METHOD: Twenty-two clinical and 18 non-clinical voice-hearers completed interviews and self-report measures assessing (1) personal goals, (2) content, characteristics, and affective reactions to voices, and (3) ratings of the extent to which voices facilitated and/or interfered with achievement of important personal goals. RESULTS: Affective reactions were strongly correlated with measures of goal interference and goal facilitation. Regression analyses revealed that these associations remained significant when controlling for important covariates (e.g., participant grouping; content, frequency and duration of voices). Goal interference was specifically associated with distress, whereas goal facilitation specifically predicted perceived pleasantness of voices. CONCLUSIONS: This study provides a novel perspective on the factors that might contribute to distress in people who hear voices. The findings suggest that perceived impact of voices on valued personal goals may be an important contributor of voice-related distress. We propose that clinical assessments, formulations, and interventions could benefit from the careful analysis of the perceived impact of voices on goals. PRACTITIONER POINTS: These findings suggest that variability in voice-related distress is closely linked to the perceived impact of voices on personal goals. These strong effects observed highlight the importance of considering the role of personal goals in future research on the psychological mechanisms leading to distress associated with voice hearing. Psychological assessments may benefit from the careful exploration of the impact of voice hearing on valued goals, and interventions promoting control over personal goals may be explored as treatment options for clients with distressing voices.

MindSurf: a pilot study to assess the usability and acceptability of a smartphone app designed to promote contentment, wellbeing, and goal achievement.

BACKGROUND: The Method of Levels (MOL) is a transdiagnostic cognitive therapy that promotes contentment, wellbeing, and goal achievement through the resolution of internal conflicts underlying psychological distress. MOL, based on Perceptual Control Theory (PCT), was developed in routine clinical practice and has been used effectively across different health services by different practitioners. Access to MOL-style questions through a smartphone app could, potentially, help both the general public maintain robust mental health, and also be a useful adjunct to therapy for clinical populations. The app is called MindSurf because of its focus on helping people explore their thinking. Prior to developing the app and using it with different populations it was necessary to determine whether such an idea would be usable for and acceptable to potential app users. Therefore, a pilot study was conducted with a non-clinical sample to assess the usability and acceptability of the app including monitoring whether the questions delivered in this way were associated with any adverse events. METHODS: A pilot study using quantitative as well as qualitative methods and incorporating a repeated measures, A-B design was conducted. RESULTS: The 23 participants were healthy adult volunteers who were all either undergraduate students, postgraduate students, or staff of the University of Manchester. They received MOL-style questions on their mobile phones over a 1-week period. Qualitative results were encouraging and indicated that the format and style of questioning were acceptable to participants and did not lead to increased worry or concern. A one-way, repeated measures ANOVA indicated that there was a nonsignificant decrease in scores on the 21-item Depression, Anxiety, and Stress Scale (DASS21) over a 2 week period. DISCUSSION: The results of the pilot study justified development of MindSurf and further testing once it is available for use. A power analysis indicated that the pilot study was underpowered to detect significant effects but provided important information regarding the appropriate sample size for future research. The pilot study also indicated that future research should investigate the effects of receiving more than three questions per day. CONCLUSION: Results of the pilot study indicate that MindSurf will be a usable and acceptable app. Its benefits should be further explored through longer studies with larger sample of both the general population as well as clinical populations.

An Introduction to Using the Method of Levels (MOL) Therapy to Work with People Experiencing Psychosis.

This paper provides a basic introduction to using method of levels (MOL) therapy with people experiencing psychosis. As MOL is a direct application of perceptual control theory (PCT), a brief overview of the three main theoretical principles of this theory--control, conflict, and reorganization will be outlined in relation to understanding psychosis. In particular, how these principles form the basis of problem conceptualisation and determine what an MOL therapist is required to do during therapy will be illustrated. A practical description of MOL will be given, using case examples and short excerpts of therapeutic interactions. Some direct contrasts will also be made with cognitive behaviour therapy for psychosis (CBTp) and psychodynamic approaches (PA) in order to help illustrate the theory and practice of MOL.

A biopsychosocial model based on negative feedback and control.

Although the biopsychosocial model has been a popular topic of discussion for over four decades it has not had the traction in fields of research that might be expected of such an intuitively appealing idea. One reason for this might be the absence of an identified mechanism or a functional architecture that is authentically biopsychosocial. What is needed is a robust mechanism that is equally important to biochemical processes as it is to psychological and social processes. Negative feedback may be the mechanism that is required. Negative feedback has been implicated in the regulation of neurotransmitters as well as important psychological and social processes such as emotional regulation and the relationship between a psychotherapist and a client. Moreover, negative feedback is purported to also govern the activity of all other organisms as well as humans. Perceptual Control Theory (PCT) describes the way in which negative feedback establishes control at increasing levels of perceptual complexity. Thus, PCT may be the first biopsychosocial model to be articulated in functional terms. In this paper we outline the working model of PCT and explain how PCT provides an embodied hierarchical neural architecture that utilizes negative feedback to control physiological, psychological, and social variables. PCT has major implications for both research and practice and, importantly, provides a guide by which fields of research that are currently separated may be integrated to bring about substantial progress in understanding the way in which the brain alters, and is altered by, its behavioral and environmental context.

Brief report: a family risk study exploring bipolar spectrum problems and cognitive biases in adolescent children of bipolar parents.

Children of parents with bipolar disorder are at increased risk of bipolar spectrum diagnoses. This cross-sectional study explores cognitive factors in the prediction of vulnerability to bipolar disorder. Adolescents at high-risk (with a parent with bipolar disorder; n = 23) and age and gender matched adolescents (n = 24) were recruited. Parent and adolescent diagnoses were evaluated (SCID and SADS-L). Adolescents completed self-report measures assessing attributional style (ASQ), appraisal of hypomania-relevant experiences (HIQ), and hypomanic personality/temperament (HPS). Despite limitations in the power of the study, significantly more adolescents at high-risk for disorder received bipolar spectrum diagnoses. Groups did not differ in attributional style, hypomanic temperament or appraisals of hypomania-relevant experiences. A trend in ASQ results and general implications are discussed. The current study suggests that familial risk of bipolar disorder is not inevitably associated with cognitive biases in adolescence.

Hypomanic personality, stability of self-esteem and response styles to negative mood.

OBJECTIVES: This paper aims to study dysfunctional self-schematic processes, abnormal coping styles, over-responsiveness to reward stimuli (indicative of an over-sensitive behavioural activation system) and stability of self-esteem in relation to subclinical hypomania. DESIGN: Three cross-sectional studies were conducted on selected students on the basis of their scores on the Hypomanic Personality Scale (HPS) (study 1) and on elevated HPS and Dysfunctional Attitude Scale scores (studies 2 and 3). METHODS: In studies 1 and 2, participants completed questionnaires and kept a self-esteem diary for 6 days. In study 3, the experience sampling method was used to assess momentary self-esteem, emotion and use of different coping styles over a 6-day period. RESULTS: Study 1 demonstrated that hypomanic traits are associated with high fluctuations in self-esteem. In study 2, high scores on both the HPS and the Dysfunctional Attitude Scale, but not the HPS alone, were associated with bipolar spectrum symptoms. These participants showed more evidence of alcohol and substance abuse, greater self-esteem fluctuation and dysfunctional coping styles (rumination and risk-taking) compared with controls. Changes in self-esteem were related to the use of these strategies. CONCLUSIONS: Vulnerability to bipolar disorder is associated with a combination of depression-related and reward-related processes.